BACKGROUND Despite widespread use of loop diuretics in congestive heart failure (HF) to achieve decongestion and relief of symptoms, as recommended by the current guidelines, there is uncertainty as to their long-term therapeutic efficacy and safety. Their efficacy and safety compared to venous ultrafiltration are currently under investigation in acute decompensated HF patients. METHODS In this article, the authors review current available data related to efficacy and safety of loop diuretics and ultrafiltration in HF. CONCLUSIONS The literature review highlights an unmet clinical need for evidence-based algorithms, potentially using not only the classical clinical signs and symptoms of congestion as well as the estimated glomerular filtration rate and serum electrolytes, but also biomarkers of congestion/decongestion, neurohumoural activation or urinary kidney injury molecules, in order to optimize both loop diuretics and renin-angiotensin-aldosterone system blocker use in HF patients.